An Integrated Approach for High-Shear Wet Granulation (HSWG) Processing of TPGS-Based Formulations: Demonstration of Process Robustness through Experimental Design Conditions.

Abstract

The goal of this study was to understand the impact of high-shear wet granulation (HSWG) processing conditions on product attributes for a tablet formulation containing the non-ionic surfactant TPGS. The use of TPGS in oral solid drug products has been reported to be challenging due to the low melting temperature of TPGS. In addition, literature on TPGS-based HSWG formulations, especially practical processing and scale-up knowledge, is limited. Presented here is an extension of this TPGS application in a tablet formulation, with a focus on the HSWG processing and scale-up across different granulators. To understand the processing space for this TPGS-based HSWG formulation, two consecutive studies were conducted with different objectives. First, an exploratory study was conducted to understand the impact of extreme processing conditions on product attributes. Subsequently, a factorial design of experiment (DoE) study assessed the separate contributions and interactions from HSWG processing variables. The outcome of both studies led to a successful process scale-up and product transfer from lab to commercial development using different granulators. The TPGS-based formulation was demonstrated to provide robust downstream processing (improved flowability and reduced segregation potential) within a wide HSWG operating space, while having a minimal impact on product performance across different granulators.